FDA Names Zocilurtatug Pelitecan Orphan Drug in Neuroendocrine Carcinomas

The FDA has granted orphan drug designation to zocilurtatug pelitecan, an investigational Delta-like ligand 3 (DLL3) antibody-drug conjugate (ADC), for the treatment of neuroendocrine carcinomas (NECs).¹

Orphan drug designation is intended to encourage development of therapies for rare diseases in the United States. The designation may provide incentives such as tax credits for qualified clinical testing, exemption from certain FDA user fees, and, if ultimately approved, up to 7 years of market exclusivity for the designated indication.

DLL3 is frequently overexpressed in NECs, including pulmonary NECs like small cell lung cancer (SCLC) as well as extrapulmonary neuroendocrine carcinomas (epNECs), making it a potential therapeutic target. Currently, there are no approved targeted therapies and no established standard of care for patients with previously treated NECs, underscoring the unmet need in this patient population.

“[Zocilurtatug pelitecan] has now received important regulatory designations around the world, signifying its potential to become an important new therapeutic option for patients with multiple types of cancer with DLL3 expressions.” Rafael G. Amado, MD, president and head of global research and development at Zai Lab, stated in a news release. “Given the need among the NEC patient community, we are focused on efficiently advancing our clinical programs for this investigational DLL3-targeting ADC.”

The FDA action follows several previous regulatory milestones for zocilurtatug pelitecan. Earlier in 2026, the FDA granted zocilurtatug pelitecan fast track designation for the treatment of extrapulmonary NECs. The agent had previously also received FDA fast track designation and orphan drug designation for SCLC, as well as orphan drug designation from the European Medicines Agency (EMA) for pulmonary NECs.

About Zocilurtatug Pelitecan and Clinical Development

Zocilurtatug pelitecan is designed to selectively target DLL3, a cell surface protein expressed on multiple neuroendocrine malignancies while demonstrating limited expression in normal tissues. The ADC delivers a cytotoxic payload directly to DLL3-expressing tumor cells, with the goal of improving antitumor activity while limiting systemic exposure.

In pulmonary NECs, zocilurtatug pelitecan is being evaluated as a treatment for relapsed SCLC in the global, randomized, open-label phase 3 DLLEVATE trial (NCT07218146) after phase 1 data (NCT06179069) showed an overall response rate (ORR) of 68% among 53 patients who received the agent as second-line therapy.²

The DLLEVATE trial is comparing the efficacy and safety of zocilurtatug pelitecan as monotherapy with investigator’s choice of therapy, with co-primary end points of confirmed ORR assessed by blinded independent central review and overall survival.³ Secondary end points include duration of response, progression-free survival, ORR per RECIST v1.1, confirmed central nervous system response, and measures of safety.

The trial is actively recruiting for an estimated total of 480 adult patients with histologically confirmed SCLC who have documented disease progression on first-line platinum-based systemic therapy across sites in the United States, Europe, and Asia. The study is projected to complete in 2028.

REFERENCES

1. U.S. FDA Grants Orphan Drug Designation to Zai Lab’s DLL3-Targeting ADC Zocilurtatug Pelitecan (Zoci) for the Treatment of Neuroendocrine Carcinomas (NECs). News release. Zai Lab Limited. August 3, 2026. Accessed August 4, 2026. https://tinyurl.com/4nm92njs

2. Zai Lab announces updated phase 1 data for zocilurtatug pelitecan (formerly ZL-1310), demonstrating potential as a first-in-class/best-in-class DLL3-targeted ADC for small cell lung cancer, and initiation of global phase 3 registrational study. Press release. Zai Laboratory. October 24, 2025. Accessed August 5, 2026. https://tinyurl.com/bd8pvz2r

3. A Study of ZL-1310 Versus Investigator's Choice of Therapy in Participants With Relapsed Small Cell Lung Cancer (DLLEVATE). ClinicalTrials.gov. Updated July 20, 2026. Accessed August 5, 2026. https://clinicaltrials.gov/study/NCT07218146